Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_004360.5(CDH1):c.1779dup (p.Ile594fs)

CA10577548

234610 (ClinVar)

Gene: CDH1
Condition: CDH1-related diffuse gastric and lobular breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 3e24a117-e2ed-4f5e-9992-bd7eac3b6454
Approved on: 2023-08-25
Published on: 2023-08-25

HGVS expressions

NM_004360.5:c.1779dup
NM_004360.5(CDH1):c.1779dup (p.Ile594fs)
NC_000016.10:g.68822068dup
CM000678.2:g.68822068dup
NC_000016.9:g.68855971dup
CM000678.1:g.68855971dup
NC_000016.8:g.67413472dup
NG_008021.1:g.89777dup
ENST00000261769.10:c.1779dup
ENST00000261769.9:c.1779dup
ENST00000422392.6:c.1596dup
ENST00000562836.5:n.1850dup
ENST00000566510.5:c.*445dup
ENST00000566612.5:c.*19dup
ENST00000611625.4:c.1842dup
ENST00000612417.4:c.1779dup
ENST00000621016.4:c.1779dup
NM_004360.3:c.1779dup
NM_001317184.1:c.1596dup
NM_001317185.1:c.231dup
NM_001317186.1:c.-187dup
NM_004360.4:c.1779dup
NM_001317184.2:c.1596dup
NM_001317185.2:c.231dup
NM_001317186.2:c.-187dup
More

Pathogenic

Met criteria codes 4
PVS1 PS4_Supporting PM5_Supporting PM2_Supporting
Not Met criteria codes 22
PS1 PS3 PS2 PP3 PP2 PP4 PP1 PM4 PM1 PM3 PM6 BA1 BS2 BS3 BS1 BS4 BP7 BP5 BP3 BP4 BP1 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen CDH1 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 3.1

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
CDH1 VCEP
The c.1779dup p.(Ile594fs) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). Additionally, this variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 15235021). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.
Met criteria codes
PVS1
Exon 12 of 16, predicted NMD.
PS4_Supporting
DGC at 33 years old (variant reported as 1779insC) (PMID: 15235021).
PM5_Supporting
Apply PM5_Supporting to nonsense/frameshift variants that are predicted/proved to undergo NMD.
PM2_Supporting
Absent in population databases.
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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